The passing of genetic material from one generation to the next, i.e. from parents to their children, is a key biological process. How this endeavor is accomplished, however, is only partially understood. We have previously found a family of proteins called the Piwi proteins to be essential for this process. To understand in more detail how Piwi works, we have identified additional proteins which interact with it. In flies, Piwi interacts with a protein called Papi;this interaction is evolutionarily conserved, as Piwi and Papi proteins in mouse and human also interact. In flies, Papi is required for proper development of the embryo and for formation of specialized cells (called germline) which pass genetic information to future generations. However, nothing is known about how it may function in vertebrates such as mice and humans. Because Papi is required for proper formation of fly embryos and their ability to transmit genetic information, and because its interaction with Piwi proteins are highly conserved, we hypothesize that this interaction is important for the function of mammalian Papi proteins. Here, we propose experiments which will test this hypothesis and determine the role of Mouse Papi (Mapi) in regulation of the germline. Specifically, we propose to 1) examine the expression patterns of Mapi during germline development and in mature gonads, 2) determine the function of Mapi during post-natal spermatogenesis, and 3) characterize Mapi protein and RNA complexes. PUBLIC HEALTH RELEVANCE: Sexually reproducing organisms, such as mice and humans, need to pass their genetic information from one generation to the next. This must be accomplished accurately, as mistakes can lead to severe health issues in the offspring, and requires highly specialized tissue in the body to do so. The experiments in this proposal will define how one protein, Mapi, contributes to this process.